7-48198243-T-C

Variant names:

• chr7-48198243-T-C
• rs374725499
• NM_152701.5:c.170T>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_152701.5(ABCA13):​c.170T>C​(p.Leu57Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000787 in 1,575,170 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000075 (0 hom.)
• Consequence: ABCA13 NM_152701.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.17
• Publications: 1 publications found

Genes affected

ABCA13 (HGNC:14638): (ATP binding cassette subfamily A member 13) In human, the ATP-binding cassette (ABC) family of transmembrane transporters has at least 48 genes and 7 gene subfamilies. This gene is a member of ABC gene subfamily A (ABCA). Genes within the ABCA family typically encode several thousand amino acids. Like other ABC transmembrane transporter proteins, this protein has 12 or more transmembrane alpha-helix domains that likely arrange to form a single central chamber with multiple substrate binding sites. It is also predicted to have two large extracellular domains and two nucleotide binding domains as is typical for ABCA proteins. Alternative splice variants have been described but their biological validity has not been demonstrated.[provided by RefSeq, Mar 2009]

ABCA13 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.858

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA13	NM_152701.5	c.170T>C	p.Leu57Ser	missense_variant	Exon 3 of 62	ENST00000435803.6	NP_689914.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA13	ENST00000435803.6	c.170T>C	p.Leu57Ser	missense_variant	Exon 3 of 62	1	NM_152701.5	ENSP00000411096.1
ABCA13	ENST00000417403.5	n.170T>C		non_coding_transcript_exon_variant	Exon 3 of 18	2		ENSP00000409268.1

Frequencies

GnomAD3 genomes AF: 0.000126 AC: 16 AN: 126564 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000791

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000103

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000245

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000487 AC: 12 AN: 246210 AF XY: 0.0000375

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000295

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000981

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000746 AC: 108 AN: 1448494 Hom.: 0 Cov.: 32 AF XY: 0.0000653 AC XY: 47 AN XY: 720210

African (AFR) AF: 0.0000300 AC: 1 AN: 33364

American (AMR) AF: 0.0000227 AC: 1 AN: 43988

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25820

East Asian (EAS) AF: 0.00 AC: 0 AN: 39210

South Asian (SAS) AF: 0.00 AC: 0 AN: 83372

European-Finnish (FIN) AF: 0.0000379 AC: 2 AN: 52798

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5724

European-Non Finnish (NFE) AF: 0.0000942 AC: 104 AN: 1104488

Other (OTH) AF: 0.00 AC: 0 AN: 59730

GnomAD4 genome AF: 0.000126 AC: 16 AN: 126676 Hom.: 0 Cov.: 31 AF XY: 0.000113 AC XY: 7 AN XY: 62078

African (AFR) AF: 0.00 AC: 0 AN: 33360

American (AMR) AF: 0.0000790 AC: 1 AN: 12658

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2942

East Asian (EAS) AF: 0.00 AC: 0 AN: 4338

South Asian (SAS) AF: 0.00 AC: 0 AN: 3908

European-Finnish (FIN) AF: 0.000103 AC: 1 AN: 9666

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 216

European-Non Finnish (NFE) AF: 0.000245 AC: 14 AN: 57166

Other (OTH) AF: 0.00 AC: 0 AN: 1668

Alfa AF: 0.000169 Hom.: 0

Bravo AF: 0.0000718

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000123 AC: 1

ExAC AF: 0.0000497 AC: 6

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.170T>C (p.L57S) alteration is located in exon 3 (coding exon 3) of the ABCA13 gene. This alteration results from a T to C substitution at nucleotide position 170, causing the leucine (L) at amino acid position 57 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.39
CADD	Uncertain	25
DANN	Uncertain	1.0
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.63	T
M_CAP	Uncertain	0.18	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Pathogenic	1.1	D
PhyloP100		4.2
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-2.0	N
REVEL	Pathogenic	0.79
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.81
MVP		0.84
MPC		0.21
ClinPred		0.33	T
GERP RS		5.3
gMVP		0.33
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs374725499; hg19: chr7-48237840;